Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Primary Purpose
Hypercholesterolemia, Insulin Resistance, Insulin Secretion
Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Lowering cholesterol concentrations by PCSK-9 inhibitor
Sponsored by
About this trial
This is an interventional basic science trial for Hypercholesterolemia
Eligibility Criteria
Inclusion Criteria:
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
- Medical indication for the treatment with a PCSK9-inhibitor
- HbA1c < 6,5%
Exclusion Criteria:
- Diabetes mellitus
- Pregnant women or breastfeeding
- Hb < 11.5 g/dl (males) or Hb < 10.5 g/dl (females)
- treatment with any medication that effects on blood glucose concentrations, e.g. antidiabetic drugs or steroids
- Any pancreatic disease
Sites / Locations
- University of Tuebingen, Department of Internal Medicine IVRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LDL lowering therapy
Arm Description
Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.
Outcomes
Primary Outcome Measures
Change in insulin secretion.
Effect of lowering LDL cholesterol levels on insulins secretion.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Secondary Outcome Measures
Change in insulin sensitivity.
Effect of lowering LDL cholesterol levels on insulin sensitivity. This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Change in insulin clearance.
Effect of of lowering LDL cholesterol levels on insulin clearance.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Change in glucose tolerance.
Effect of lowering LDL cholesterol levels on glucose tolerance assessed by 75g oral glucose tolerance test
Full Information
NCT ID
NCT04314167
First Posted
March 10, 2020
Last Updated
August 24, 2022
Sponsor
University Hospital Tuebingen
1. Study Identification
Unique Protocol Identification Number
NCT04314167
Brief Title
Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Official Title
Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2020 (Actual)
Primary Completion Date
March 15, 2023 (Anticipated)
Study Completion Date
June 15, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. It is well established that statin/PCSK9-inhibitor treatment is very effective in lowering LDL cholesterol levels and therefore in preventing cardiovascular events. Besides the beneficial effects on cardiovascular system, these therapies are unfortunately linked to increased risk for type 2 diabetes.
However underlying mechanisms for the association between LDL cholesterol levels and the risk for type 2 diabetes remains largely unknown.Type 2 diabetes is especially characterized by insulin resistance and impaired insulin secretion from pancreatic beta-cells. Insulin resistance alone is insufficient to cause type 2 diabetes, as long as the ß-cell is able to compensate for the increased demand for insulin. Once this compensatory mechanism reaches its physiological limits, individuals progress to type 2 diabetes. Accordingly we aimed to investigate the associations between LDL cholesterol concentrations and the key issue in the pathogenesis of type 2 diabetes, insulin secretion before and after lowering cholesterol concentration by treatment with Evolocumab for 12 weeks in patients with medical indication for a treatment with a PCSK9-inhibitor. Therefore, patients will either undergo a hyperglycemic clamp or a oral glucose tolerance test in randomized manner.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Insulin Resistance, Insulin Secretion
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LDL lowering therapy
Arm Type
Experimental
Arm Description
Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.
Intervention Type
Drug
Intervention Name(s)
Lowering cholesterol concentrations by PCSK-9 inhibitor
Intervention Description
Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.
Primary Outcome Measure Information:
Title
Change in insulin secretion.
Description
Effect of lowering LDL cholesterol levels on insulins secretion.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Time Frame
before and after 12 weeks of treatment with a PCSK9-inhibitor.
Secondary Outcome Measure Information:
Title
Change in insulin sensitivity.
Description
Effect of lowering LDL cholesterol levels on insulin sensitivity. This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Time Frame
before and after 12 weeks of treatment with a PCSK9-inhibitor.
Title
Change in insulin clearance.
Description
Effect of of lowering LDL cholesterol levels on insulin clearance.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Time Frame
before and after 12 weeks of treatment with a PCSK9-inhibitor.
Title
Change in glucose tolerance.
Description
Effect of lowering LDL cholesterol levels on glucose tolerance assessed by 75g oral glucose tolerance test
Time Frame
before and after 12 weeks of treatment with a PCSK9-inhibitor.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
Medical indication for the treatment with a PCSK9-inhibitor
HbA1c < 6,5%
Exclusion Criteria:
Diabetes mellitus
Pregnant women or breastfeeding
Hb < 11.5 g/dl (males) or Hb < 10.5 g/dl (females)
treatment with any medication that effects on blood glucose concentrations, e.g. antidiabetic drugs or steroids
Any pancreatic disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreas Fritsche, Prof.
Phone
0049 (0)7071-29 80590
Email
andreas.fritsche@med.uni-tuebingen.de
Facility Information:
Facility Name
University of Tuebingen, Department of Internal Medicine IV
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Fritsche, Prof
Phone
+49 7071 29 80590
Email
andreas.fritsche@med.uni-tuebingen.de
12. IPD Sharing Statement
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Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
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